Bleomycin-induced chromosomal aberrations in Epstein-Barr virus-transformed human lymphoblastoid cells

• Published in: Mutation research. Genetic toxicology and environmental mutagenesis 2024-10, Vol.899, p.503823, Article 503823
• Main Authors: Cardozo, Andrea G., Castrogiovanni, Daniel C., Bolzán, Alejandro D.
• Format: Article
• Language: English
• Subjects: Antibiotics, Antineoplastic - pharmacology; Antibiotics, Antineoplastic - toxicity; Bleomycin - pharmacology; Bleomycin - toxicity; Cell Line; Cell Line, Transformed; Cell Transformation, Viral - drug effects; Chromosome Aberrations - chemically induced; Chromosome Aberrations - drug effects; Herpesvirus 4, Human - drug effects; Herpesvirus 4, Human - genetics; Humans; incomplete chromosome elements; Lymphocytes - drug effects; Lymphocytes - virology; PNA-FISH; terminal acentric fragment
• ISSN: 1383-5718; 1879-3592
• DOI: 10.1016/j.mrgentox.2024.503823

We have evaluated the induction of complete (i.e., without open ends) and incomplete (i.e., with non-rejoined or open ends) chromosomal aberrations by the radiomimetic antibiotic bleomycin (BLM) in human lymphoblastoid cells immortalized with the Epstein-Barr virus (EBV). An EBV-induced lymphoblastoid cell line (T-37) was exposed to BLM (10–200 µg/mL) for 2 h at 37ºC, and chromosomal aberrations were analyzed 24 h after treatment, using PNA-FISH with pan-telomeric and pan-centromeric probes. Both complete (multicentrics, rings, compound acentric fragments, and interstitial deletions) and incomplete (incomplete chromosomes or IC, and terminal acentric fragments or TAF) chromosomal aberrations increased significantly in BLM-exposed cells, although the concentration-response relationship was non-linear. Of the acentric fragments (ace) induced by BLM, 40 % were compound fragments (CF, ace +/+). TAF (ace, +/-) and interstitial fragments (IAF, ace -/-) were induced at similar frequencies (30 %). 230 ICE were induced by BLM, of which 52 % were IC and 48 % TAF. The average ratio between total incomplete chromosome elements (ICE) and multicentrics was 1.52. These findings suggest that human lymphoblastoid cells exhibit less repair capacity than human lymphocytes, with respect to BLM-induced ICE, and that chromosomal incompleteness is a common event following exposure of these cells to BLM. •Bleomycin is a radiomimetic antibiotic widely used in clinical chemotherapy.•Telomere plus centromere PNA-FISH detects incomplete chromosome elements.•Bleomycin induces incomplete chromosome elements in human lymphoblastoid cells.•Bleomycin induced incomplete chromosome elements more than multicentrics, in human lymphoblastoid cells.